The epidemiological evidence is insufficient to support a causal relationship between bladder cancer and long-term exposure to chlorinated drinking-water, THMs, chloroform or other THM species. The epidemiological evidence is inconclusive and equivocal for an association between colon cancer and long-term exposure to chlorinated drinking-water, THMs, chloroform or other THM species. The information is insufficient to allow an evaluation of the observed risks for rectal cancer and risks for other cancers observed in single analytical studies.

Various types of epidemiological studies have attempted to assess the cancerrisks that may be associated with exposure to chlorinated drinking-water. Chloraminated drinking-water was considered in two studies. Several studies have attempted to estimate exposures to total THMs or chloroform and the other THM species, but the studies did not consider exposures to other DBPs or other water contaminants, which may differ for surface water and groundwater sources. One study considered the mutagenicity of drinking-water as measured by the Salmonella typhimurium assay. Assessments of possible cancer risks that may be associated with drinking-water disinfected with ozone or chlorine dioxide have not been performed.

Ecological and death certificate-based case-control studies have provided hypotheses for further evaluation by analytical studies that consider an individual's exposure to drinking-water and possible confounding factors.

Analytical studies have reported weak to moderate increased relative risks of bladder, colon, rectal, pancreatic, breast, brain or lung cancer associated with long-term exposure to chlorinated drinking-water. Single studies reported associations for pancreatic, breast or brain cancer; however, the evaluation of a possible causal relationship for epidemiological associations requires evidence from more than a single study. In one study, a small increased relative risk of lung cancer was associated with the use of surface water sources, but the magnitude of risk was too small to rule out residual confounding.

A case-control study reported a moderately large association between rectal cancer and long-term exposure to chlorinated drinking-water or cumulative THM exposure, but cohort studies have found either no increased risk or a risk too weak to rule out residual confounding.

Decreased bladder cancer risk was associated with increased duration of exposure to chloraminated drinking-water, but there is no biological basis for assuming a protective effect of chloraminated water.

Although several studies found increased risks of bladder cancer associated with long-term exposure to chlorinated drinking-water and cumulative exposure to THMs, inconsistent results were reported among the studies for bladder cancer risks between smokers and non-smokers and between men and women. Estimated exposure to THMs was considered in three of these studies. In one study, no association was found between estimated cumulative exposure to THMs. In another study, a moderately strong increased relative risk was associated with increased cumulative exposure to THMs in men but not in women. The third study reported a weak increased relative risk associated with an estimated cumulative exposure of 1957-6425 µg of THMs per litre-year; weak to moderate associations were also reported for exposure to THMconcentrations greater than 24, greater than 49 and greater than 74 µg/litre. No increased relative risk of bladder cancer was associated with exposure to chlorinated municipal surface water supplies, chloroform or other THM species in a cohort of women, but the follow-up period of 8 years was very short, resulting in few cases for study.

Because inadequate attention has been paid to assessing exposure to water contaminants in epidemiological studies, it is not possible to properly evaluate the increased relative risks that were reported. Specific risks may be due to other DBPs, mixtures of by-products or other water contaminants, or they may be due to other factors for which chlorinated drinking-water or THMs may serve as a surrogate.

Results of early studies are difficult to interpret because of methodological limitations or suspected bias.

A recently completed but not yet published case-control study has reported moderate increased relative risks for neural tube defects in children whose mothers' residence in early pregnancy was in an area where THM levels were greater than 40 µg/litre. Replication of the results in another area is required before this association can be properly evaluated. A previously conducted study in the same geographic area reported a similar association, but the study suffered from methodological limitations.

A recently reported cohort study found an increased risk of early miscarriage associated with heavy consumption of water (five or more glasses of cold tapwater per day) containing high levels (>75 µg/litre) of THMs. When specific THMs were considered, only heavy consumption of water containing BDCM (>18 µg/litre) was associated with a risk of miscarriage. As this is the first study to suggest an adverse reproductive effect associated with a brominated by-product, a scientific panel recommended that another study be conducted in a different geographic area to attempt to replicate these results and that additional efforts be made to evaluate exposures of the cohort to other water contaminants.